Smooth Muscle Dysfunction Syndrome (SMDS)
Conditions
Keywords
smooth muscle aortic alpha-actin (ACTA2), arginine 179 residue, Nicotinamide Riboside, Stroke, Cerebrovascular Disease, Thoracic Aortic Aneurysms and Dissections
Brief summary
The purpose of this study is to determine whether SMDS patients treated with NR at the proposed dose exhibit decreased glucose uptake in the aorta, to determine if NR treatment results in measurable changes of blood NAD+ and NR levels, to determine if aortic measurements are stable after treatment with NR and to evaluate the safety and tolerability of NR in SMDS patients.
Interventions
Participants will take their weight-based dose of NR once daily by mouth with food for 60 days.
Sponsors
The University of Texas Health Science Center, Houston
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Individuals diagnosed with SMDS with confirmed ACTA2 mutation disrupting arginine 179 * Parental/guardian permission (informed consent) and, if appropriate, child assent.
Exclusion criteria
* Individuals who have undergone surgery to replace aneurysmal or dissected ascending and root aortic tissue with a graft. * Additional medical conditions that impair the patient's ability to participate in the study. * Known allergy or sensitivity to niacin or nicotinamide riboside. * Prior consumption of niacin or nicotinamide riboside supplement within the prior eight weeks. * Failure to provide informed consent. * Concurrent participation in another intervention trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Aortic diameter as assessed by the echocardiography | Baseline , 8 weeks | — |
| Change in cognitive function as assessed by the NIH Toolbox assessment | Baseline , 8 weeks | NIH Toolbox assessment evaluates multiple domains of cognitive performance including executive function, attention, episodic memory, language, processing speed, and working memory. Individual test scores are combined into a composite cognition score and reported as age-adjusted T-scores (mean = 50, SD = 10), where higher scores indicate better cognitive function. |
| Change in autonomic symptoms as assessed by the Composite Autonomic Symptom Score 31 (COMPASS-31) survey | Baseline , 8 weeks | This is a 31 item questionnaire and each is scored from 0 (no symptoms) to 100(maximum symptom burden), with higher scores indicating more severe autonomic dysfunction. |
| Change in Impact of headaches as assessed by the Headache Impact Test (HIT-6) questionnaire | Baseline, 8 weeks | HIT-6 questionnaire consists of 6 questions, each scored from 6(never) to 13(always), with total scores ranging from 36 to 78. Higher scores indicate a greater impact of headaches on quality of life. |
| Pulmonary function tests (PFTs), including spirometry and lung volume measurements | Baseline, 8 weeks | — |
| Change in systolic blood | Baseline , 8 weeks | — |
| Change in cerebral oxygenation and perfusion as assessed by the Head-up tilt table testing (HUTT) with near-infrared spectroscopy (NIRS) monitoring. | Baseline , 8 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Change in Levels of NR in whole blood as measured by high-performance liquid chromatography (HPLC) | Baseline , 8 weeks |
| Safety as assessed by number of participants that show drug toxicity as shown in bloodwork | Baseline |
| Tolerability as assessed by the number of patients who complete study | end of study( 8 weeks after baseline) |
| Change in Levels of Nicotinamide adenine dinucleotide (NAD+) in whole blood as measured by high-performance liquid chromatography (HPLC) | Baseline , 8 weeks |
Countries
United States
Contacts
Primary ContactDianna M Milewicz, MD, PhD
Backup ContactDavid R Murdock, MD
Outcome results
None listed